Osteopontin


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OPN structure

References

The thermal stability is described by the loss rate. Packages Simulation. Quality Guarantee. Instruction Manual. If the antibody is used in flow cytometry, please check FCM antibodies. Magazine Citations Journal of Biomedical Materials Research Part A Proliferation and osteogenesis of immortalized bone marrow-derived mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture PubMed: Osteoarthritis and Cartilage Elevated osteopontin level of synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis patients PubMed: The Journal of Rheumatology Thrombin-cleaved osteopontin levels in synovial fluid correlate with disease severity of knee osteoarthritis.

Ebscohost Am J Pathol. Catalog No. Proliferation and osteogenesis of immortalized bone marrow-derived mesenchymal stem cells in porous polylactic glycolic acid scaffolds under perfusion culture PubMed: Elevated osteopontin level of synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis patients PubMed: Thrombin-cleaved osteopontin levels in synovial fluid correlate with disease severity of knee osteoarthritis.

Arrows indicate known cleavage sites for thrombin and MMPs. Thrombin cleavage site in blue and MMPs cleavage site in green. OPN regulates the immune system at many different levels. It serves as a chemotactic molecule to promote the migration of inflammatory cells to the wound site and acts as an adhesive protein to retain cells at the site.

alphabetical listing

OPN also functions as a pro-inflammatory cytokine and can modulate the immune response by enhancing expression of Th1 cytokines and matrix degrading enzymes Weber et al. OPN plays a pivotal role in T cell and macrophage responses during cell mediated immune responses against bacterial and viral pathogens Ashkar et al. More recently, OPN has also been shown to modulate dendritic cell responses and neutrophil chemotaxis.

OPN is not expressed in circulating monocytes, but is dramatically upregulated during macrophage differentiation and constitutes one of the major macrophage products Krause et al. Functionally OPN plays a key role in macrophage biology by regulating migration, survival, phagocytosis, and pro-inflammatory cytokine production Bruemmer et al. We and others have shown that OPN serves as a potent chemoattractant for macrophages Bruemmer et al.

Functional inhibition of OPN and genetic ablation of OPN in mice greatly impair macrophage recruitment in several models of acute inflammation.

Osteopontin and the immune system: another brick in the wall

In OPN-null mice acute macrophage infiltration was greatly diminished compared to wild-type mice in an obstructed kidneys model Ophascharoensuk et al. Further, purified OPN induced macrophage accumulation when injected in rat dermis and following intradermal injection of N-formyl-met-leu-phe FMLP , a potent macrophage chemotactic peptide.

In a rat model of heart injury OPN was highly expressed in the granulation tissue associated macrophages, and it was downregulated with healing progression and formation of the fibrotic scar Murry et al. Wound healing studies in mice also indicate that OPN is expressed during the acute inflammatory phase at very high levels in infiltrating leukocytes and other cell types where it appears to regulate leukocyte infiltration and activation as well as proper matrix organization Liaw et al.

Interestingly, downregulation of OPN at the wound site with antisense mRNA diminished macrophage infiltration and accelerated wound healing Mori et al. OPN also modifies chronic inflammatory responses.

Chronic inflammation is characterized by the persistence of macrophages at sites of injury and disease. Deficits in macrophage accumulation have been noted in OPN-null mice when challenged with chronic inflammatory conditions, including atherosclerosis, delayed-type hypersensitivity Yu et al. These data suggest that OPN may be particularly important in promoting migration and retention of macrophages at sites of acute and chronic inflammation.

In a recent paper we described that despite the defect in macrophage recruitment, OPN-null mice formed more FBGCs on the surface of the implant. This may be a consequence of a lack of a permissive pro-migratory substrate, and the reduced expression of CD44 observed in OPN-null macrophages. CD44 is well known to be essential for macrophage migration Marcondes et al. Macrophages from OPN-null mice are also more susceptible to programmed cell death Bruemmer et al. Together with impaired migration, macrophage apoptosis may further contribute the impaired macrophage accumulation observed in OPN-null mice in response to acute and chronic inflammatory stimuli.

In addition to regulating macrophage migration, OPN can also modulate the cytokine production by macrophages.

Species Glossary

Interestingly, these results were mediated by different receptors. In this model, Bruemmer at al. These results correlated with less macrophage rich lesions and lower expression of the macrophage marker CD68 Bruemmer et al. While OPN is generally classified as a pro-inflammatory cytokine, it also appears to have anti-inflammatory effects.

Osteopontin/OPN Products: R&D Systems

OPN represses inducible nitric oxide synthase iNOS by increasing Stat1 ubiquitination and proteasome mediated degradation of Stat1, consequently inhibiting Stat1 mediated iNOS transcription and protein expression Gao et al. Finally, a recent study suggests that OPN may play a role in macrophage differentiation. Further, OPN silenced cells had decreased expression of macrophage scavenger receptor A type 1 Msr-1 , a macrophage differentiation marker. While these studies are intriguing, the phenotype could not be rescued by the addition of exogenous OPN suggesting non-receptor mediated effects or iOPN may be involved.

Together, these data suggest that OPN may be particularly important in promoting migration and retention of macrophages at sites of acute and chronic inflammation by regulating multiple macrophage functions. While much is known about the role of OPM in macrophage biology, relatively few studies have explored the function of OPN in neutrophils.

Neutrophils express low levels of OPN Koh et al. However, OPN is important for the recruitment and migration of neutrophils, as neutrophils from OPN-null mice display reduced chemotaxis toward fMLP and in vivo the recruitment of neutrophils to the peritoneal cavity in response to sodium periodate is impaired in OPN-null mice Koh et al.

OPN-null mice also have impaired neutrophil infiltration into liver when challenged with concanavalin A induced hepatitis Diao et al. Despite these defects in migration and chemotaxis, OPN-null neutrophils do not display reduced destructive capacity in terms of phagocytosis, the generation of reactive oxygen species, or cytokine production Koh et al.

OPN is also known as Eta-1 early T lymphocyte activation gene 1 for its high expression in activated T cells and it plays an important role in the induction of cell mediated immune responses through the regulation of T cells. The development of Th1 cells leads to cell-mediated immunity while development of Th2 cells provides humoral immunity. Th17 cells are associated with autoimmunity. Shinohara et al. In vivo , OPN-null mice display impaired Th1 responses to the intracellular bacterium Listeria monocytogenes and the viral pathogen HSV1 herpes simplex virus type 1 both of which depend on the induction of IL for protection Ashkar et al.

Together these findings suggest that OPN may play a role in polarizing early Th1 responses. This appears to be important for the progression of experimental autoimmune encephalomyelitis EAE , a murine model of multiple sclerosis. Finally, a subset of lymphocytes bridging innate and adaptive immunity called invariant natural killer T iNKT cells has also been shown to be regulated by OPN. Diao et al. This appeared to be consequence of impairment of intrathymic iNKT cell maturation and significant alteration of iNKT cell function as well Diao et al.

OPN plays a key role in DC maturation, migration, and polarization. During macrophage differentiation, OPN expression increases as monocytes adhere and differentiate into macrophages Krause et al. In vivo , DCs in OPN-null mice display a defect in DC trafficking to the lymph nodes resulting in reduced contact hypersensitivity responses Weiss et al. Recently, it has also been suggested that OPN modulates different subset of DCs in the airway hypersensitivity reaction a model of asthma.

It appears that OPN increased the reaction during primary sensitization but decreased the reaction in the challenge phase, perhaps by mediating differential recruitment of different DCs plamacytoid and conventional subsets to the lymph nodes Xanthou et al. OPN also influences DC cytokine production. OPN is a key cytokine regulating tissue repair.

OPN is present at sites of wound healing where it serves as a chemotactic molecule to recruit inflammatory cells to the site of injury. Compared to wild type mice, incisional wounds made in OPN-null mice displayed alterations in the matrix architecture especially collagen fiber diameter, and had more residual debris Liaw et al. Furthermore, macrophages at the wound site in OPN-null mice expressed higher levels of mannose receptor, suggesting OPN may contribute to macrophage polarization and thus regulate healing responses.

A more recent study by Mori et al. Consistent with the finding in OPN-null mice, in OPN knockdown wounds the diameter of collagen fibrils was also smaller than in control wounds. Further, OPN knockdown hindered the migration of inflammatory cells to the wound site and resulted in accelerated healing and a reduction in granulation tissue formation and scarring Mori et al. Whether the infiltrated macrophages in OPN knockdown wounds also had a less pro-inflammatory and more pro-healing phenotype was not established, however, this may be behind the observed accelerated healing.

These studies indicate a role for OPN in promoting proper collagen organization and regulating ECM and myofibroblast interactions. To date, several studies have investigated the role of OPN in the progression of atherosclerosis. Bone marrow transplantation studies in an angiotensin II-accelerated model of atherosclerosis indicated that leukocyte derived OPN contributes to OPN mediated development of atherosclerosis Bruemmer et al.

These studies suggest that OPN promotes macrophage accumulation and retention in the atherosclerotic lesions, thus contributing to the chronicity of the disease. OPN also modulates other vascular cells associated with vascular disease. In human atherosclerotic lesions, OPN is expressed in smooth muscle cells SMC , angiogenic endothelial cells, and macrophages and it is re-expressed in SMCs associated with human restenotic lesions Giachelli et al. All these data indicate that during injury, OPN enhances the proliferation, migration, and accumulation of smooth muscle and endothelial cells involved in repair and remodeling processes of the vasculature.

OPN is highly expressed in transformed cells and is found in a variety of cancers Wai and Kuo OPN overexpression can confer metastatic phenotype to non-metastatic, benign transformed cells, and increased OPN expression correlates with tumor progression, poor prognosis and increased invasiveness. Thus, the ability of OPN to stimulate migration and matrix breakdown could contribute to invasiveness and to the metastatic potential of tumors cells.

Human Osteopontin (OPN) Protein, His Tag

OPN may also promote tumorigenesis and metastasis by inhibiting apoptosis of tumor cells Zhao et al. Finally, OPN is widely expressed by macrophages, which infiltrate tumor tissue Brown et al. Macrophage-derived OPN functions as a chemoattractant and was associated with reduced tumor burden while tumor-derived OPN appeared to inhibit macrophage function and enhance tumor growth Crawford et al. OPN is currently being studied as a potential biomarker for cancer and there is interest in targeting OPN as a therapeutic treatment for cancer.

OPN is one of the most abundant non-collagenous proteins in bone. Because of its abundance in bone, OPN has been studied as a regulator of biomineralization. OPN is a potent inhibitor of mineralization, prevents ectopic calcification, and is an inducible inhibitor of vascular calcification Steitz et al. OPN binds hydroxyapatite and calcium ions thereby physically inhibiting crystal formation and growth in vivo.

OPN also plays a role in osteoclast differentiation and osteoblast recruitment and function Rittling et al. OPN functions in osteoclast migration to sites of resorption and is crucial for normal resorption and bone turnover Chellaiah et al. OPN appears also to be an important regulator of vascular calcification and is associated with mineralized deposits in humans Giachelli et al. Vascular calcification is now recognized as a marker of atherosclerotic plaque burden as well as a major contributor to loss of arterial compliance and increased pulse pressure seen with age, diabetes, and renal insufficiency.

These findings suggest that OPN may be an important inhibitor of arterial mineral deposition under conditions of injury and disease, and that strategies to replenish OPN might be useful to prevent or treat ectopic calcification, including vascular calcification. OPN is emerging as a key regulator of immune cell biology. Most of the evidence indicates that OPN is transiently expressed in leukocytes during acute inflammation. However, persistence of OPN expression by immune cells exacerbates chronic inflammatory diseases. Mechanistically, OPN appears to regulate innate immune cells macrophages and DCs and adaptive immune cells T cells at multiple levels see Fig.

Recent data point to a role for OPN in the regulation of cross-talk between DCs and T cells and their subsequent polarization in Th1 and more recently in Th17 cells.

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